International Publication No. WO 89/05812 discloses a thienodiazepine compound having an antagonistic action on cholecystokinin and gastrin.
Cholecystokinin (also referred to as CCK) is a neuropeptide consisting of 33 amino acids, and CCK-8 which consists of 8 amino acids at the C terminus also reveals activity. Gastrin consists of 34 amino acids, and pentagastrin which consists of 5 amino acids at the C terminus also shows activity. The amino acid sequence of pentagastrin is identical with that at the C terminus of CCK. Both exist in gastrointestinal tissues and the central nervous system, and are concerned with the control of pancreatic enzyme secretion and gastric acid secretion.
Since the substances which exhibit an antagonistic action on CCK and gastrin are effective in the prophylaxis and therapy of such diseases as pancreatic disorders and gastrointestinal ulcers, a number of such antagonistic substances have been studied so far. Also, it has recently been reported that the antagonistic action on CCK is related to an anti-dementia action.
As an antagonistic substance to CCK, benzotripto is known [Proc. Natl. Acad. Sci. U.S.A., vol. 78, p. 6304 (1981)], and proglumide is known as an antagonistic substance to gastrin [J. Med. Chem., vol. 27, p. 1597 (1984)]. Their actions are, however, relatively weak, and compounds having higher activities have been desired.
Besides, peptide antagonistic substances are not entirely satisfactory in that the durability of their actions is short and in that they are unstable and poorly absorbed.